Life-extending ovarian cancer chemotherapy underused, study finds

Patients with non-metastatic ovarian cancer live an average of 16 months longer when chemotherapy is delivered into the abdomen instead of by standard intravenous infusion, yet only a minority of eligible patients are receiving it, report scientists from Dana-Farber Cancer Institute.

The use of intraperitoneal (IP) chemotherapy shot up after the National Cancer Institute issued a rare alert in 2006 recommending IP chemotherapy as the new standard of care, said Alexi Wright, MD, MPH a medical oncologist in the Susan F. Smith Center for Women’s Cancers at Dana-Farber. She will reveal the findings in a poster presentation at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago on Saturday, May 31, 2014.

But after rising from 15 percent in 2005 to 50 percent in 2007, use of IP chemotherapy in eligible ovarian cancer patients did not increase further and may have dropped slightly, reported Wright. Her study is the first to examine whether physicians are using IP chemotherapy in clinical practice at six comprehensive cancer centers.

Strikingly, Wright found that when providers are using IP therapy, they often change the chemotherapy given, an indication that patients are not receiving the chemotherapy that proved so effective in clinical trials. In more than 40 percent of cases, providers reduced doses or substituted less toxic chemotherapy drugs, Wright reported. “Oncologists may have lowered the dose of chemotherapy to make the treatment easier for patients,” said Wright, citing the difficulty that many patients had completing treatment on the landmark clinical trial. “However, this poses other risks to patients because in the past decreasing doses of chemotherapy has come at the cost of lower survival rates.”

Surprisingly, even with substandard application of IP chemotherapy, patients who received IP chemotherapy lived longer than those given intravenous chemotherapy: IP chemotherapy was associated with a five-year survival rate of 62.5 percent compared with 45.0 percent for intravenous therapy.

Because IP chemotherapy is more toxic and requires experienced surgeons and supportive care providers, it is most often carried out at major centers such as those belonging to the National Comprehensive Cancer Center Network (NCCN), said Wright. But when the study examined use of IP chemotherapy in eligible patients at six NCCN centers, it found a wide range of use between centers, 16 percent to 71 percent.

“We were surprised to find this huge variation between institutions,” said Wright. “It’s hard to believe that there was this level of difference between what patients wanted at each institution. Rather, it suggests that physicians’ preferences or institutional biases may have decided what care patients were offered—a troubling finding since this treatment is associated with a major survival benefit.”

The study wasn’t designed to identify and measure what factors contribute to the variation in use of IP chemotherapy, and Wright called for further research on these questions.

The patients in the study had stage III disease that had spread beyond the ovaries but had not reached the liver or lungs.

The recommended protocol calls for surgical removal, or “debulking,” of all of the tumors larger than 1 centimeter. Then the patient receives six cycles of IP chemotherapy, with prescribed doses of two drugs, cisplatin and paclitaxel, over 18 weeks. The drugs are delivered through a catheter surgically implanted into the peritoneum, a fluid-filled hollow space enclosed by membranes that contains the abdominal organs.

Patients undergoing this treatment were more likely to have complications related to the implanted catheter, according to the report. They experienced double the rate of adverse effects such as dehydration, low blood counts and anemia, and were twice as likely to discontinue therapy for these reasons as were patients on IV chemotherapy.

“Despite this, IP is associated with significant improved survival in clinical practice,” she said, “suggesting that the mechanism of chemotherapy delivery matters.”